‘How have you been feeling lately?’ A simple question with a not-so-simple response, especially for people with mental health illnesses. Mental health conditions are very prevalent globally, yet most people do not have access to appropriate care.
The World Health Organization (WHO) reported that one in eight people are affected by mental disorders, whereas a recent study by Harvard Medical School and the University of Queensland showed that half of the world’s population will develop a mental disorder in their lifetime.
The Covid-19 pandemic played a double-edged sword role in the mental health space. While the prevalence of mental health disorders increased, it also raised awareness. “If there is any silver lining from the pandemic, it is that [there is less] stigma of having mental health disorders that require care and attention, and people are less worried about having a conversation about not being okay,” says Shawn Singh, CEO at Vistagen.
Yet, clinical trials that recruit these patients face multifactor challenges. From finding the right participants to providing needed additional support, researchers and trial sponsors must identify the right strategies to successfully recruit for their trials.
Lack of diagnosis halts recruitment
The first challenge in recruiting patients with mental health disorders is accurate diagnosis. Dr Lindsey Matt, clinical quality supervisor at Lyra Health and a member of technology provider Medable’s Patient Caregiver Network, says via email to Clinical Trials Arena that individuals may not have a formal diagnosis or self-identify with terms such as ‘depressed’ or ‘anxious’ due to stigma or lack of knowledge.
While stigma plays a crucial role in diagnosing mental disorders, which may defer in every country, different ways of receiving a diagnosis may also affect an individual’s response to research. For example, men from black and minority ethnic (BME) backgrounds disproportionately get their mental health diagnosis through the criminal justice system, says Dr Adwoa Parker. Parker, who is UK’s National Institute for Health and Care Research (NIHR) advanced fellow at the University of York, adds that this can lead to a lack of trust in authorities and being suspicious about services.
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Surprisingly, even clinicians can act as barriers. Parker says that a doctor or a nurse may not extend the invite to their patient who is invited to a trial because they may assume the patient is not well or capable enough to participate. “There is a sense of paternalism,” she notes.
Improving recruitment in trials
Recruiting this patient population requires a thoughtful and patient-centric approach that addresses the challenges and the needs of this patient population, explains Boehringer Ingelheim’s Christine Sakdalan, vice president of the mental health franchise, and Dr Michael Jablonski, vice president of clinical development and medical affairs, via email. They add that this can be done by working with mental health clinics, hospitals and advocacy partners who can support awareness of clinical trials.
Telephone follow-ups of people who were invited to a clinical trial but did not respond can also help. Parker explains that people are more likely to participate in a trial if their doctor calls them up and asks if they have any questions about the invitation.
As for the clinical trial staff, investigators need to be trained on how to discuss mental health in a direct and respectful way, says Matt. Parker adds that clinical trial teams should be more inclusive to reflect the actual patient population. Clinical Trials Arena previously reported how diverse staff may overcome diversity issues in trials.
It is also important to consider the value of participation for the potential subject. Singh explains that open-label extension opportunities could be an incentive for mental health patients. The extension would allow the participant to remain on the medication even after the trial is over.
The role of technology
With the rise of decentralised clinical trials (DCTs), the role of decentralisation and technology is yet to be determined in mental health clinical trials, Parker notes. While remote appointments may be enough for some patients, others may need to see someone in person. “It is important to understand that within the context of each population group and work out what is feasible,” she adds.
Certain decentralisation elements can expand access to a broader portion of patients with various mental health conditions, Jablonski and Sakdalan explain. For example, outcome assessments can be completed by a mobile nurse from the privacy of the participant’s home or the use of digital technologies such as telemedicine can reduce geographical constraints.
However, there must be regular in-person touch points to stay on top of any potentially emerging safety concerns, Singh notes. Additionally, not all trial designs lend themselves to decentralisation. For example, Vistagen is using a public speaking challenge in several of its Phase III trials in social anxiety disorder. Such design requires in-person execution and could not be done remotely, he says.
Participation in other indication trials
As previously discussed, one of the main participation barriers in mental health trials is formal diagnosis, but this issue can also affect non-mental health clinical trials. Matt explains that it is more than likely that people with mental health conditions are already enrolled into trials where they usually would be excluded. The reason is that they do not meet the full criteria for a mental health condition or they do not have access to the diagnosis.
Moreover, stringent inclusion and exclusion criteria in clinical trials often do not represent the real-world population. “At the end of the day, the treatments will be given to people in the real world and a large proportion of people will have underlying health conditions, including mental health problems,” says Parker.
Such exclusion of relevant participants may allow for a drug to enter the market without knowing its full effect on the majority of the potential real-world patients. This was seen with Novo Nordisk’s GLP-1 receptor agonists for diabetes and obesity such as Ozempic and Wegovy (semaglutide), and Saxenda (liraglutide).
In July, the European Medicines Agency (EMA) and UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) started investigations over reports of allegedly increased suicidal or self-harming thoughts in patients who took Novo Nordisk’s GLP-1 receptor agonists. In September, NPR reported that clinical trials investigating Ozempic screened for depression, anxiety and suicidal thoughts, resulting in the exclusion of patients with these conditions. However, between 20% and 60% of people with obesity live with a mental disorder, while people with diabetes are two to three times more likely to have depression.
A similar issue could be observed in Parkinson’s disease, Matt notes. It is estimated that 30-40% of patients with Parkinson’s also have depression. “If a study were to exclude those with depression, they would miss a significant portion of the patient population who may benefit from the medication or intervention being researched,” she says.
Overall, while the awareness around mental health is increasing, mental health research still needs to take many steps towards better medication. Singh says that this space needs innovation and drugs with a new mechanism of action that are clearly differentiated from the current standard of care that comes with many side effects that are as frustrating to manage as the underlying condition. Also, mental health disorders need to be addressed like physical illnesses with a clear treatment pathway. “We need a game plan,” Singh adds.